This proposal is divided into two sets of experimental approaches designed to provide a better understanding of gene regulation in developmental systems. In these studies SV40, polyoma and the adenoviruses are used as probes to elucidate viral host range limitations in teratocarcinoma cells and alter cellular gene expression by studying the production of cellular tumor antigens after virus infection. Host range restrictions - polyoma and SV40 express their early proteins in most mouse cells in culture. Both viruses fail to produce these proteins in murine embryonal carcinoma cells (EC cells) which are the stem cells of teratocarcinomas. Studies to date indicate that EC cells infected with these viruses either fail to transcribe the early viral genes or fail to process the viral nuclear RNA into spliced m-RNA species. Experiments are designed to study the mechanism of this host range restriction 1) at the level of transcription and RNA processing, 2) a study of the RNA polymerase II from EC cells, 3) the isolation of virus host range mutants that grow on EC cells, 4) temperature-sensitive EC cells host range restriction, 5) a survey of EC cell restrictions and virus. 2) EC cells and papovavirus-infected and -transformed cells express high levels of a cellular protein that is specifically immunoprecipitated by sera from animals bearing SV40-induced tumors. This cellular tumor antigen is physically complexed with SV40 large T antigen in solution. Experiments are designed to 1) study the nature of this complex with purified proteins, 2) examine the effect of the cellular antigen on T-antigen DNA binding and enzymatic activity, 3) isolate mutants in the gene coding for this cellular tumor antigen, 4) study the expression of this cellular protein in developmental systems, and 5) characterize additional tumor antigens recently detected in EC cells and transformed cells.